Clinical Immunology Flashcards
SPUR
Suspect immunocompromised if any of... Severe infection Persistent infection Unusual infecting agent Recurrent infection
Hyper IgM
Group of immunodeficiency syndromes characterised by failure to class switch
Therefore high or normal levels IgM - low levels IgG / IgA
Antenatal diagnosis possible
Relatives of T cell immunodeficiency
Classification of immunodeficiencies
Primary - defects on gene(s) - even if unknown
Secondary - acquired - environmental factors
Most immunodeficiencies…
NOT primary
Approx 1/100,000 have primary immunodeficiency
Most secondary, often doctors are direct cause
Secondary immunodeficiency causes
Infections eg HIV Malignancies (and their treatments) Extremes of age Drugs - toxins, corticosteroids Chronic disease and nephrotic syndrome
Drugs as immunosuppressants
Cyclosporine, tacrolimus, rapamycin
Anti - TNFa therapies
Depleting mAb - rituximab
Chronic lymphocytic leukaemia treatment induces AIDS like state
Recurrent infections which may NOT imply identifiable immunodeficiency
Otitis media (>5 years as cut off) UTI Group A streptococcus Staphylococcal furuncles Dental carries HSV (genital)
Indications for investigation immunocompromised
>2 systemic bacterial infections >3 respiratory / other specific site bacterial infection Infection at unusual site Infection with unusual pathogen Unusually severe infection with low virulence organisms / unusual complication Past surgery for infection >2 months antibiotics with little effect Failure to thrive in infancy
Classification of primary immunodeficiency
Almost half are just antibody About 1/4 phagocytes Some cellular Some complement About 1/4 combined
B cell deficiency can result in
Bacterial infections of all types
T cell deficiency results in…
Mainly viruses, fungi, intracellular bacteria
Bacterial infections if severe
Complement deficiency results in…
Encapsulated bacteria
Eg neisseria meningitides
Haemophilia influenzae
Streptococcus pneumoniae
Phagocyte deficiency results in…
Fungi
Mycobacteria
Specific bacteria inc. salmonella, burkholderia
IgA deficiency
1:700 (Caucasians)
Respiratory, gut infection, coeliac disease
Major reactions to blood product
Worse if also IgG subclass deficiency
IgG subclass deficiency
IgG1/3 - effects response to protein antigens
IgG2 - response to polysaccharides
IgG4 - no consensus on significance, normal range can be 0
Common variable immunodeficiency (CVID) prevelence
Heterogenous group disorders
Core feature IgG deficiency
20-50 per million
Lifelong, 20% have family history
CVID disease manifestations
Recurrent sino-pulmonary infections
Granulomatous disease
Autoimmunity & cytopenias
X linked agammaglobulinaemia
Defect in Bruton’s tyrosine kinase, no heavy chain rearrangement
No B cells,lymphoid tissue, immunoglobulin
Present at 6 months +, antenatal diagnosis possible
Total - absence of Igs and antibodies
Infections in antibody deficient states - recurrent and persistent
Recurrent - otitis media, sinusitis, pneumonia, bacteraemia
Persistent - rotavirus, girsrdia, enterovirus
Transient infantile hypogammaglobulinaemia
Dip around 4 months, corrected by 6 months
Decrease in maternal IgG, while still low rate of endogenous production
Normal
Treating antibody deficiency
Immunoglobulin transfusion - pooled, screened
Iv or subcutaneous
Severe combined immunodeficiency (SCID)
Unwell by 3 months
Persistent diarrhoea, failure to thrive
Infections of all types inc. unusual skin disease
Family history of early infant death
DiGeorge Syndrome
Pure T cell defect
Branchial arch defects
- hypoparathyroidism, aortic arch defects, thymol aplasia, dysmorphic
Translocation chromosome 22
PNP deficiency
Pure T cell deficiency
Progressive decrease T cell numbers
